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Common genetic variants located in calcium channel genes are important markers of genetic susceptibility for bipolar disorder (BD). Previous clinical trials with Calcium Channel Blocker (CCB) medication improved mood stability for some BD patients. We hypothesize that manic patients who carried calcium channel risk variants would differentially benefit from treatment with CCBs. In this pilot study, 50 BD patients (Chinese: 39; US: 11) who were hospitalized for manic episodes were given add-on CCB treatment. We determined genotypes for each patient. There was a significant decrease in the Young Mania Rating Scale (YMRS) after add-on medication treatment. Of note, two intronic variants of the Calcium Voltage-Gated Channel Subunit Alpha1 B (CACNA1B) were associated with treatment outcomes for manic patients: rs2739258 and rs2739260. BD rs2739258/rs2739260 AG-allele carriers had a better treatment response with add-on CCB than those carrying the AA or GG genotypes by survival analysis. Although these findings did not pass multiple testing correction, this study suggests that single-nucleotide polymorphisms (SNPs) residing in calcium channel genes could be predictors for response to add-on CCB treatment of bipolar mania patients, and that calcium channel genes may be involved in treatment responses for BD., Competing Interests: Declaration of Competing Interest Financial or personal interests or beliefs that could affect the authors’ objectivity, or potential competing interests, do not exist., (Copyright © 2023. Published by Elsevier B.V.)

Schizophrenia (SCZ) and bipolar disorder (BPD) are associated with abnormal expression of immune-related factors (IRFs), which have been proposed as biomarkers of either disease diagnosis (trait markers) or treatment (state markers). However, the state markers have been found to be less reproducible than the trait markers in previous studies. In the current study, we focused on the changes of IRFs in blood of SCZ and BPD patients receiving monotherapy. SCZ (N = 49) and BPD (N = 49) Chinese patients were recruited at acute episode and followed for 9 to 51 days until remission. Blood samples were collected at two state-points, acute state before treatment and remission state after treatment. A total of 41 IRFs in plasma were quantified by the Luminex assay. After adjusting covariates, we found four cytokines or cytokine receptors were significantly increased at remission when compared to acute episode in all the patients, including CD30, BAFF, CCL20, and CXCL10 (Bonferroni corrected p < 0.05). CD30 and BAFF were consistently increased in both SCZ and BPD while the increase of CCL20 was only observed in BPD but not SCZ when analyzing the two disorders separately. CXCL10 change was not significant in either SCZ or BPD alone. The changes of these four factors were correlated with each other, but not with clinical features. CD30 concentration in the BPD acute state was correlated with sleep quality (Spearman's r s  = 0.365, Bonferroni corrected p < 0.05). Overall, we found that four factors (CD30, BAFF, CCL20, and CXCL10) might be associated with treatment of psychosis., (© 2022. The Author(s).)

Highlights from the article: B Background: b Cell type diversity is the basis of complex brain functions, also psychiatric disorders. B Methods: b We used bulk tissue RNA-Seq data of 413 prefrontal cortex samples including healthy controls and patients with schizophrenia (SCZ) and bipolar disorder (BD) from PsychENCODE/BrainGVEX project. B Discussion: b We extracted cell type-specific expression from bulk brain tissues and examined the cell-specific alternation in psychiatric disorders regarding cell composition, gene expression, genetic regulation and their functional variation.